The proposed research is a continuation of studies on the mechanism of phosphate transfer in the phosphoglucomutase system. The areas of immediate emphasis are as follows: a. Determination of the role of the metal ion in the reaction. NMR techniques will be used in studies of the structural relationship between enzyme-bound Mn2 ion, Co2 ion and Ni2 ion and metal-binding ligands of the protein, the phosphate-group of the phospho-enzyme, and nucleii present in the substrate and a series of inhibitors. b. An examination of possible structural alterations in the enzyme accompanying the conversion of the phospho- and dephospho- forms of the enzyme and differences in structural changes produced in the two forms of the enzyme by metal binding will be made; such studies will involve CD, ORD and UV difference spectral measurements. C. An evaluation of the thermodynamics of phosphate transfer within the ternary enzyme-metal-glucose phosphate complex by use of radio-tracer studies. d. An investigation of the elementary aspects of crystal structure of phosphoglucomutase by x-ray diffraction studies. e. A preliminary investigation of the properties of frog muscle and rat diaphragm phosphoglucomutase to determine the feasibility of physiological studies of the Zn2 ion/Mg2 ion free ion ratio in these tissues by utilizing the properties of their endogenous phosphoglucomutases.